ECE2022 Oral Communications Oral Communications 14: Late Breaking (6 abstracts)
Discovery of microRNA biomarkers in circulation and bone tissue from a type-2 diabetes mellitus rat model under different anti-osteoporotic treatments
David Carro Vázquez 1 , Lejla Emini 2 , Martina Rauner 2 , Christine Hofbauer 2 , Johannes Grillari 3 , Richard Eastell 4 , Lorenz C Hofbauer 2 & Matthias Hackl 1
1TAmiRNA GmbH, Wien, Austria; 2Dresden University of Technology, Department of Medicine III and Center for Healthy Aging, Dresden, Germany; 3Ludwig Boltzmann Institut, Department of Experimental and Clinical Traumatology, Wien, Austria; 4The University of Sheffield, Academic Unit of Bone Metabolism, and Mellanby Centre for Bone Research, Sheffield, United Kingdom
Metabolic changes in Type-2 Diabetes-Mellitus (T2DM) make patients more prone to develop osteoporosis and delayed bone healing. We hypothesize that microRNAs could be involved in the underlying mechanism and used as biomarkers in this context. To test this hypothesis, we analyzed microRNAs in samples from Zucker Diabetic Fatty (ZDF) rats, a T2DM model with reduced bone healing and bone mass. 11-week-old male ZDF and wildtype rats with a femur subcritical defect were treated with placebo, anti-sclerostin, PTH and insulin treatments for 12 weeks. After the treatment, metabolic and bone phenotype parameters of all the rats were measured and serum and ulna samples were obtained (n= 4-5 per group). RNA isolation and small RNA next generation sequencing (NGS) were performed using serum and ulna samples for untargeted genome-wide miRNA analysis. Significantly (adj. P<0.2) regulated miRNAs identified by NGS were further analyzed with the online tool miRnet 2.0 for miRNA target network construction and with the FANTOM5 browser for cell-type enrichment analysis. Our results show that insulin induced a strong dysregulation of circulating miRNAs mainly involved in metabolism, and even rescued seven circulating miRNAs in the ZDF model (rno-miR-802-5p, rno-miR-122-3p, rno-miR-375-3p, rno-miR-27a-5p, rno-miR-31a-5p, rno-miR-192-5p, rno-miR-122-5p). Anti-sclerostin caused a less intense miRNA dysregulation in serum but affected miRNAs shown to be enriched in bone tissue, rescuing particularly one of those miRNAs (rno-miR-145-5p). PTH treatment did not produce any effect on circulating neither on bone miRNAs in the ZDF rats, most probably due to a blunting effect of diabetes over the PTH. Altogether, this study shows the enhancement effect on bone mass and bone regeneration potentially caused by dysregulation of bone miRNAs and of the rescue of circulating miRNAs in ZDF rats under the three analyzed treatments.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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